Role of alteration/deficiency in activation (ADA) complex in cell cycle, genomic instability and cancer

Shakur Mohibi, Shashank Srivastava, Hamid Band, Vimla Band

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations

Abstract

In eukaryotes, DNA wraps around histone proteins to form highly condensed chromatin structures that usually remain inert and inaccessible to proteins involved in DNA-related processes. Thus, multitudes of important DNA-related biological processes, including transcription, replication, DNA repair, apoptosis, chromosome condensation, and segregation, are dependent upon alteration of this chromatin structure so that proteins involved in these processes can access the DNA. This required change in chromatin structure is brought about by binding of various chromatin modifying proteins that loosen the chromatin by distinct mechanisms, one of which is covalent histone modification. Various histone post-translational modifications, specifically acetylation, play a major role in opening up of this highly condensed chromatin allowing access to proteins involved in the several important processes. Histone acetyl transferases (HATs) and histone deacetylases (HDACs) are important for maintaining a steady-state level of this particular post-translational modification in cells and are present in multi-subunit complexes. One such multi-subunit HAT complex is the alteration/deficiency in activation (ADA) complex, which was originally discovered in yeast and is now known to be also present in mammalian cells as part of much larger HAT complexes. In this chapter, we discuss various components of the ADA complex with a special focus on the adaptor proteins Ada3 and Ada2 (Ada2a and Ada2b) for their role in important physiological processes, such as the cell cycle, genomic integrity, DNA repair response, and in pathology such as cancer. Further, we discuss recent developments using various inhibitors to target the HAT enzymes and disrupt HAT complex function as an anti-cancer strategy.

Original languageEnglish (US)
Title of host publicationNuclear Signaling Pathways and Targeting Transcription in Cancer
PublisherHumana Press Inc.
Pages33-55
Number of pages23
ISBN (Print)9781461480389
DOIs
StatePublished - 2014

Publication series

NameCancer Drug Discovery and Development
Volume88
ISSN (Print)2196-9906
ISSN (Electronic)2196-9914

Keywords

  • Ada2
  • Ada3
  • Cancer
  • Cell cycle
  • DNA repair
  • HAT inhibitors
  • HATs
  • Nuclear receptors
  • p53
  • Viral oncogenes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Drug Discovery

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